Proton Pump Inhibitors Linked to Risk for Heart Failure, Death in CAD

Proton pump inhibitors (PPIs) may increase the risk for heart failure and death, but not acute ischemic events, in patients with coronary artery disease (CAD), according to a study published in PLoS One.

Chronic antiplatelet therapy in patients with CAD carries the risk for gastrointestinal (GI) complications, such as such GI ulcers and hemorrhage with aspirin and impaired healing of aspirin-induced gastric erosions with clopidogrel. PPIs are commonly used to prevent or treat these GI complications, but PPI use may lead to pneumonia, micronutrient deficiencies, and osteoporosis-related fractures. In addition, limited data suggest PPI use may inhibit the antiplatelet effect of aspirin and clopidogrel and lead to more cardiovascular events in patients with CAD.

The researchers investigated the relationship between PPI use and adverse cardiovascular outcomes in patients with CAD in a prospective cohort study.

A total of 706 patients enrolled had adequate follow-up data and blood samples for analysis. Of these, 431 were treated with PPIs, most commonly omeprazole. Approximately two-thirds of all patients were taking clopidogrel, and more than 90% were taking aspirin.

The primary end point was the combination of the secondary outcomes, which were acute ischemic events (eg, myocardial infarction or stroke) and all-cause heart failure or death.

More patients receiving PPIs met the primary outcome than those not receiving PPIs (14.61% vs 5.45%; hazard ratio [HR], 2.281; P =.008).

Other predictors for the primary outcome included body mass index, atrial fibrillation, and hypertension.

PPI use increased the risk for all-cause heart failure or death (HR, 5.713; P =.007), but not for acute ischemic events.

“The present work shows that PPI use is an independent predictor of [heart failure] or death. Although there are no previous studies reporting this association, it is known that pantoprazole may exert negative inotropic effects on isolated myocardium from humans and rabbits,” the researchers wrote. However, data regarding the effect of PPIs on myocardial function are limited and conflicting.

“In conclusion, our results suggest an association between use of PPIs and the incidence of death or [heart failure] but do not point to an association with incidence of acute ischemic events. More studies are needed to confirm these data,” the researchers wrote.

Reference

Pello Lázaro AM, Cristóbal C, Franco-Peláez JA, et al. Use of proton-pump inhibitors predicts heart failure and death in patients with coronary artery disease. PLoS One. 2017;12(1):e0169826. doi: 10.1371/journal.pone.0169826